Fisetin

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Fisetin
Fisetin structure
Identifiers
CAS number 528-48-3 YesY
PubChem 5281614
ChemSpider 4444933 YesY
DrugBank DB07795
KEGG C10041 YesY
ChEBI CHEBI:42567 YesY
ChEMBL CHEMBL31574 YesY
Jmol-3D images Image 1
Properties
Molecular formula C15H10O6
Molar mass 286.2363 g/mol
Density 1.688 g/mL
Melting point 330 °C
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
 YesY (verify) (what is: YesY/N?)
Infobox references
Not to be confused with Cotinine.

Fisetin is a flavonol, a structurally distinct chemical substance that belongs to the flavonoid group of polyphenols. It can be found in many plants, where it serves as a colouring agent. Its chemical formula was first described by Austrian chemist Josef Herzig in 1891.[1] Possible anti-aging, anti-inflammatory, anti-cancer, and anti-viral properties of fisetin are under active scientific investigation.

Biological activity[edit]

Fisetin is a potent sirtuin-activating compound (STAC),[2] an agent that modulates sirtuins. Therefore, it is a caloric restriction mimetic candidate, a drug that has been shown to be able to alleviate aging effects in certain model organisms, such as the yeast S. cerevisiae,[2] the nematode C. elegans[3] and the fruit fly Drosophila melanogaster.[3] Whether such effects can be replicated in humans and other mammals is currently still not entirely clear and remains an issue of scientific research and debate.

Aside from its effects on aging, various in vitro studies have shown fisetin to exert anti-inflammatory,[4][5] anti-carcinogenic,[6][7] and antiviral[8][9][10][11] effects in different lines of culture cells. However, because in vitro experiments do not or only incompletely mimic fisetin metabolism in the body, they may not accurately reflect the actual effects of fisetin in vivo. During absorption through the small intestine and passage through the liver, fisetin and other flavonoids undergo chemical modifications such that their form in circulating blood is different from that in the original dietary source.[12]

Similar to many other flavonoids, such as the structurally related flavonol quercetin, fisetin is a potent antioxidant. Its antioxidative activity may be due to its structural properties[13] as well as to its ability to modulate certain cellular signalling pathways, especially protein kinase and lipid kinase pathways. For example, fisetin has been shown to induce the transcription factor Nrf2,[14] leading to increased expression of several protective and antioxidative genes. In one study of a genetic mouse model of Type 1 diabetes known as the Akita mouse, large oral doses of fisetin were associated with reduced kidney hypertrophy, reduced anxiety, and lower levels of oxidative stress markers.[15] Feeding fisetin to wild-type mice, though, had no apparent effect.[15]

Biological sources[edit]

Fisetin can be found in a wide variety of plants. It is found in Eudicotyledons, such as trees and shrubs in the family Fabaceae, such as the acacias Acacia greggii[16] and Acacia berlandieri,[16] the parrot tree (Butea frondosa), the honey locust (Gleditsia triacanthos), members of the family Anacardiaceae such as the Quebracho colorado and species of the genus Rhus, which contains the sumacs.[17] Along with myricetin, fisetin provides the color of the traditional yellow dye young fustic, which was extracted from the Eurasian smoketree (Rhus cotinus). Many fruits and vegetables also contain fisetin,[18] including strawberries[15][19] apples,[19] and grapes.[19][20] Fisetin can be extracted from fruit and herbal sources in juices, wines,[21] and infusions such as teas.[20] It is also found in Monocotyledons such as onions.[19] It is also present in Pinophyta species such as the yellow cypress (Callitropsis nootkatensis).

Side effects[edit]

Fisetin was, among other flavonoids, found to be a strong topoisomerase inhibitor.[22] This effect may be responsible for both anticarcinogenic and carcinogenic potentials of the substance.[23] As DNA topoisomerase inhibitors, fisetin and other flavonoids may increase risk of infant acute myeloid leukemia, a rare disease.[24]

References[edit]

  1. ^ Herzig, J. (1891). "Studien über Quercetin und seine Derivate, VII. Abhandlung" [Studies on Quercetin and its Derivatives, Treatise VII]. Monatshefte für Chemie (in German) 12 (1): 177–90. doi:10.1007/BF01538594. 
  2. ^ a b Howitz, Konrad T.; Bitterman, Kevin J.; Cohen, Haim Y.; Lamming, Dudley W.; Lavu, Siva; Wood, Jason G.; Zipkin, Robert E.; Chung, Phuong et al. (2003). "Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan". Nature 425 (6954): 191–6. doi:10.1038/nature01960. PMID 12939617. 
  3. ^ a b Wood, Jason G.; Rogina, Blanka; Lavu, Siva; Howitz, Konrad; Helfand, Stephen L.; Tatar, Marc; Sinclair, David (2004). "Sirtuin activators mimic caloric restriction and delay ageing in metazoans". Nature 430 (7000): 686–9. doi:10.1038/nature02789. PMID 15254550. 
  4. ^ Geraets, Liesbeth; Haegens, Astrid; Brauers, Karen; Haydock, Jane A.; Vernooy, Juanita H.J.; Wouters, Emiel F.M.; Bast, Aalt; Hageman, Geja J. (2009). "Inhibition of LPS-induced pulmonary inflammation by specific flavonoids". Biochemical and Biophysical Research Communications 382 (3): 598–603. doi:10.1016/j.bbrc.2009.03.071. PMID 19292976. 
  5. ^ Park, Hyo-Hyun; Lee, Soyoung; Son, Hee-Young; Park, Seung-Bin; Kim, Mi-Sun; Choi, Eun-Ju; Singh, Thoudam S. K.; Ha, Jeoung-Hee et al. (2008). "Flavonoids inhibit histamine release and expression of proinflammatory cytokines in mast cells". Archives of Pharmacal Research 31 (10): 1303–11. doi:10.1007/s12272-001-2110-5. PMID 18958421. 
  6. ^ Lim, D. Y.; Park, J. H. Y. (2009). "Induction of p53 contributes to apoptosis of HCT-116 human colon cancer cells induced by the dietary compound fisetin". AJP: Gastrointestinal and Liver Physiology 296 (5): G1060–8. doi:10.1152/ajpgi.90490.2008. 
  7. ^ Khan, N.; Afaq, F.; Syed, D. N.; Mukhtar, H. (2008). "Fisetin, a novel dietary flavonoid, causes apoptosis and cell cycle arrest in human prostate cancer LNCaP cells". Carcinogenesis 29 (5): 1049–56. doi:10.1093/carcin/bgn078. PMC 2902387. PMID 18359761. 
  8. ^ Zandi, K.; Teoh, B. T.; Sam, S. S.; Wong, P. F.; Mustafa, M.; Abubakar, S. (2011). "Antiviral activity of four types of bioflavonoid against dengue virus type-2". Virology Journal 8: 560. doi:10.1186/1743-422X-8-560. PMC 3271998. PMID 22201648.  edit
  9. ^ Lin, Y. J.; Chang, Y. C.; Hsiao, N. W.; Hsieh, J. L.; Wang, C. Y.; Kung, S. H.; Tsai, F. J.; Lan, Y. C.; Lin, C. W. (2012). "Fisetin and rutin as 3C protease inhibitors of enterovirus A71". Journal of Virological Methods 182 (1–2): 93–98. doi:10.1016/j.jviromet.2012.03.020. PMID 22465253.  edit
  10. ^ Kang, S. Y.; Kang, J. Y.; Oh, M. J. (2012). "Antiviral activities of flavonoids isolated from the bark of Rhus verniciflua stokes against fish pathogenic viruses in Vitro". The Journal of Microbiology 50 (2): 293–300. doi:10.1007/s12275-012-2068-7. PMID 22538659.  edit
  11. ^ Lyu, S. Y.; Rhim, J. Y.; Park, W. B. (2005). "Antiherpetic activities of flavonoids against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in vitro". Archives of pharmacal research 28 (11): 1293–1301. PMID 16350858.  edit
  12. ^ Kroon, P. A.; Clifford, M. N.; Crozier, A.; Day, A. J.; Donovan, J. L.; Manach, C.; Williamson, G. (2004). "How should we assess the effects of exposure to dietary polyphenols in vitro?". The American journal of clinical nutrition 80 (1): 15–21. PMID 15213022.  edit
  13. ^ Williams, Robert J; Spencer, Jeremy P.E; Rice-Evans, Catherine (2004). "Flavonoids: Antioxidants or signalling molecules?". Free Radical Biology and Medicine 36 (7): 838–49. doi:10.1016/j.freeradbiomed.2004.01.001. PMID 15019969. 
  14. ^ Hanneken, A.; Lin, FF; Johnson, J; Maher, P (2006). "Flavonoids Protect Human Retinal Pigment Epithelial Cells from Oxidative-Stress-Induced Death". Investigative Ophthalmology & Visual Science 47 (7): 3164–77. doi:10.1167/iovs.04-1369. PMID 16799064. 
  15. ^ a b c Maher, Pamela; Dargusch, Richard; Ehren, Jennifer L.; Okada, Shinichi; Sharma, Kumar; Schubert, David (2011). "Fisetin Lowers Methylglyoxal Dependent Protein Glycation and Limits the Complications of Diabetes". In Deli, Maria A. PLoS ONE 6 (6): e21226. doi:10.1371/journal.pone.0021226. PMC 3124487. PMID 21738623. Lay summaryScienceDaily (June 28, 2011). 
  16. ^ a b Forbes TDA, Clement BA. "Chemistry of Acacia's from South Texas" (PDF). Texas A&M Agricultural Research and Extension Center at. Retrieved 2010-04-14. 
  17. ^ Gábor, M.; Eperjessy, E. (1966). "Antibacterial Effect of Fisetin and Fisetinidin". Nature 212 (5067): 1273. doi:10.1038/2121273a0. PMID 21090477. 
  18. ^ Fiorani, M.; Accorsi, A. (2005). "Dietary flavonoids as intracellular substrates for an erythrocyte trans-plasma membrane oxidoreductase activity". The British journal of nutrition 94 (3): 338–345. PMID 16176603.  edit
  19. ^ a b c d Arai, Y.; Watanabe, S.; Kimira, M.; Shimoi, K.; Mochizuki, R.; Kinae, N. (2000). "Dietary intakes of flavonols, flavones and isoflavones by Japanese women and the inverse correlation between quercetin intake and plasma LDL cholesterol concentration". The Journal of nutrition 130 (9): 2243–2250. PMID 10958819.  edit
  20. ^ a b Viñas, P.; Martínez-Castillo, N.; Campillo, N.; Hernández-Córdoba, M. (2011). "Directly suspended droplet microextraction with in injection-port derivatization coupled to gas chromatography–mass spectrometry for the analysis of polyphenols in herbal infusions, fruits and functional foods". Journal of Chromatography A 1218 (5): 639–646. doi:10.1016/j.chroma.2010.12.026. PMID 21185565.  edit
  21. ^ De Santi, C.; Pietrabissa, A.; Mosca, F.; Pacifici, G. M. (2002). "Methylation of quercetin and fisetin, flavonoids widely distributed in edible vegetables, fruits and wine, by human liver". International journal of clinical pharmacology and therapeutics 40 (5): 207–212. PMID 12051572.  edit
  22. ^ Olaharski, A.J.; Mondrala, S.T.; Eastmond, D.A. (2005). "Chromosomal malsegregation and micronucleus induction in vitro by the DNA topoisomerase II inhibitor fisetin". Mutation Research/Genetic Toxicology and Environmental Mutagenesis 582 (1–2): 79–86. doi:10.1016/j.mrgentox.2005.01.002. PMID 15781213. 
  23. ^ López-Lázaro, Miguel; Willmore, Elaine; Austin, Caroline A. (2010). "The dietary flavonoids myricetin and fisetin act as dual inhibitors of DNA topoisomerases I and II in cells". Mutation Research/Genetic Toxicology and Environmental Mutagenesis 696 (1): 41–7. doi:10.1016/j.mrgentox.2009.12.010. PMID 20025993. 
  24. ^ Spector, L. G.; Xie, Y; Robison, LL; Heerema, NA; Hilden, JM; Lange, B; Felix, CA; Davies, SM et al. (2005). "Maternal Diet and Infant Leukemia: The DNA Topoisomerase II Inhibitor Hypothesis: A Report from the Children's Oncology Group". Cancer Epidemiology Biomarkers & Prevention 14 (3): 651–5. doi:10.1158/1055-9965.EPI-04-0602. PMID 15767345.